Carboxylesterase-Expressing Allogeneic Neural Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas

Running, not enrolling · Phase 1

Conditions studied: Recurrent Anaplastic Astrocytoma, Recurrent Anaplastic Oligoastrocytoma, Recurrent Anaplastic Oligodendroglioma, Recurrent Glioblastoma, Recurrent Gliosarcoma, Recurrent Malignant Glioma, Recurrent WHO Grade III Glioma

In brief

This phase I trial studies the side effects and best dose of carboxylesterase-expressing allogeneic neural stem cells when given together with irinotecan hydrochloride in treating patients with high-grade gliomas that have come back. Placing genetically modified neural stem cells into brain tumor cells may make the tumor more sensitive to irinotecan hydrochloride. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboxylesterase-expressing allogeneic neural stem cells and irinotecan hydrochloride may be a better treatment for high-grade gliomas.

Key facts

Study ID: NCT02192359
Run by: City of Hope Medical Center
People needed: 18
Starts: 2016-04-05
Expected to finish: 2026-09-25
Last updated by the study team: 2026-05-11

Who can join

Age: 18 and older, up to 69. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patient must be able to understand and be willing to sign a written informed consent document
Participant must be willing to comply with study and/or follow-up procedures
Karnofsky performance status >= 70%
Life expectancy of >= 3 months
Histologically-confirmed diagnosis of a grade III or IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma), or has a prior, histologically-confirmed, diagnosis of a grade II glioma and now has radiographic findings consistent with a high-grade glioma (grade III or IV)
Imaging studies show evidence of recurrent tumor(s); if a patient is going to be enrolled to dose level two or higher, the patient must have a component of supratentorial disease (so as to enable placement of a Rickham reservoir/catheter) that is amenable to resection or biopsy
High-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
Participant must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy
Based on the neurosurgeon?s judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
Neurosurgeon finds the prospective participant is able to undergo neurosurgery
Any number of prior therapies is permitted; from the start of study treatment, the following time periods must have elapsed: 6 weeks from nitrosourea-containing chemotherapy, 4 weeks from non-nitrosourea-containing cytotoxic chemotherapy (except 23 days from last daily dose of temozolomide taken in a 5 of 28 day regimen), and 2 weeks from last dose of a targeted agent (except 4 weeks for bevacizumab); there is no time period requirement for prior radiation therapy
Any clinically significant toxicity from prior therapy must have improved to grade 0 or grade 1
Absolute neutrophil count (ANC) >= 1,500 cells/ul
Platelets > 100,000 cells/ul
Total bilirubin =< 2.0 mg/dl
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times institutional upper limit of normal
Serum creatinine =< 1.5 x the institutional upper limit of normal
Homozygous negative for the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT 1A1)*28 allele
Absence anti-human leukocyte antigen (HLA) antibodies specific for HLA class I antigens expressed by the coagulation factor III (thromboplastin, tissue factor) (F3).cytosine deaminase (CD).carboxylesterase (CE) NSCs
Negative serum pregnancy test (women of childbearing potential only)
Agreement by females of childbearing potential and sexually active males to use an effective method of contraception while participating in this study; women of childbearing potential must have a negative pregnancy test < 2 weeks prior to registration

You may not qualify if…

Prior therapy with neural stem cells
Use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers including hepatic enzyme-inducing anticonvulsants (phenytoin, fosphenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) within 2 weeks prior to start of study treatment
Use of moderate to strong CYP3A4 inhibitors within 2 weeks prior to start of study treatment
Use of drugs known to inhibit UGT1A1, such as atazanir, gemfibrozil, indinavir, or ketoconazole, within 2 weeks prior to start of study treatment
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrolimus; consult principal investigator for questions, including necessary washout period for the specific drug
Flucytosine within 2 weeks prior to start of study treatment
Use of herbal medications
Current use (or planned use during the treatment period) of other investigational agents, or biological, chemotherapy, radiation or other anti-tumor therapy
Patient has known human immunodeficiency virus (HIV) or hepatitis C infection; baseline testing for HIV or hepatitis C is not required
Prospective participant is unable to undergo a magnetic resonance imaging (MRI) with contrast agent
Known chronic or active viral infections of the central nervous system (CNS)
Clinically significant uncontrolled illness
Active infection requiring antibiotics
Diagnosis of Gilbert?s disease
History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan
Known sensitivity to any of the products to be administered during dosing
Any other active malignancy
Pregnant women and women who are lactating
Serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where it is running

City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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